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1. Disease Information

1.1 General Disease and Pathogen Information: Monkeypox (MPX) is an infectious 

zoonotic disease caused by the monkeypox virus (MPXV) which is known to affect

several susceptible mammals including certain rat species, squirrels, rabbits, prairie 

dogs, new- and old-world monkeys and apes, and a variety of other species. Further 

research is needed to better define the mammalian host range. MPX is endemic to 

western and central Africa where two viral clades persist. In humans, viruses in Clade

II tend to produce mild clinical signs while viruses in Clade I have increased virulence1.

In endemic areas, monkeypox virus is thought to be maintained in nature through 

circulation in wild rodents (including squirrels and certain rat species), with occasional 

spill-over to non-human primates and humans.

MPXV can be transmitted through direct contact with an infected animal or 

contaminated materials including saliva, urine, feces, and meat. Direct human-tohuman transmission has been documented through close physical contact as well as 

respiratory droplets. Although some animal species are known to be susceptible, each 

suspected animal case, particularly for species not previously demonstrated to be 

susceptible to infection, may need additional testing to determine the true infection 

status given the lack of information available for the current circulating virus.

1.2 Clinical Signs:

1.2.1 Non-human Primates: The primary clinical sign is a self-limited rash, initially 

presenting as small cutaneous papules that develop into pustules and crust over. 

Lesions appear with an erythemic, necrotic center surrounded by epidermal 

hyperplasia and often scar after healing. There is a large variation in the number 

of pox lesions between primates; however, the most common locations to 

observe lesions is on the face, limbs, palms, soles, and tails. Rash may be 

accompanied by fever, lymphadenopathy and, in severe cases, respiratory 

signs, ocular discharge, facial edema, and anorexia. 

1.2.2 Rodents: Clinical signs include fever, anorexia, blepharoconjunctivitis, 

depression, respiratory signs, diarrhea, and cutaneous lesions. Rarely, oral 

ulcers and lymphadenopathy is observed as well. Some species of rodents 

display only nonspecific clinical signs such as lethargy, conjunctivitis, and

unkempt coat, while others are asymptomatic. African rodents are believed to be 

reservoir hosts; however, specific species have not been identified.

1 WHO now refer to the former Congo Basin (Central African) clade as Clade one (I) and the former West African 

clade as Clade two (II). Additionally, it was agreed that the Clade II consists of two subclades.

Case Definition

Monkeypox (MPX)

(Notifiable) October 2022
Animal and Plant Health Inspection Service | Veterinary Services | 2

1.2.3 Other species: more research or observational reporting is needed to define 

clinical signs.

2. Laboratory Criteria

2.1 Agent Isolation and Identification: Collect vesicle fluid by syringe and needle or 

swab ruptured vesicles, also collect any available scabs from older vesicles. If no skin 

lesions are present and there are alternative reasons to test, such as direct exposure 

to a case or viremia is suspected, collection of whole of blood in a purple top (EDTA) 

vacutainer tube. Mucocutaneous secretion, oropharyngeal or rectal swabs may be 

warranted. Keep samples as cold as possible without freezing. Tests include 

histopathology or electron microscopy, real-time polymerase chain reaction (rtPCR), 

genetic sequencing, immunohistochemistry (IHC), and virus isolation (VI).

2.2 Agent Characterization: Genome sequencing is available to differentiate viral clades

and support genomic epidemiology.

2.3 Serology: Serological tests including virus neutralization and ELISA are available for 

detecting antibodies to orthopoxviruses. Currently, there are no assays specific to 

detecting MPXV antibodies; as such, the available diagnostic and epidemiologic 

information should be used when interpreting results. 

3. Case Definition2 and Reporting Criteria

3.1 Suspect Case:

3.1.1 an animal having clinical signs consistent with MPX; AND

3.1.2 an epidemiologic link to a confirmed human or animal MPX case, or other 

exposure of public and animal health concern.

3.2 Presumptive Positive Case: an animal with a non-negative screening laboratory test 

result for MPX (Histopathology, electron microscopy, IHC, Ab ELISA, rtPCR)

3.3 Confirmed Positive Case3;4

:

3.3.1 an animal from which MPXV has been isolated; OR

3.3.2 identification of MPXV by rtPCR5 AND genomic sequencing.

2 Given the re-emerging nature of this disease laboratories should select test(s) appropriate for the sample type 

and interpret results in the context of all available information for each case.

3 Confirmatory testing must be conducted at either the Centers for Disease Control and Prevention (CDC) Poxvirus 

laboratory or the National Veterinary Services Laboratories (NVSL), Ames Iowa laboratory. 4 An animal may be excluded as a confirmed case if any of the following applies:

• An alternative diagnosis can explain the illness fully. Factors that may be considered when assigning 

alternate diagnoses include the strength of the epidemiologic evidence for disease-specific exposure, 

the specificity of the alternate diagnostic test, and the compatibility of the clinical presentation and 

course of illness for the alternative diagnosis. 

• Test result(s) are poorly or not repeatable, and resampling is either not possible, or testing from 

resampling is negative. 

• Surface contamination cannot be ruled out with available case information and test results.

5 If sufficient specimen volume is not available genomic sequencing will be prioritized and may be considered 

confirmatory if sequence of sufficient quality is obtained.